NM_172107.4(KCNQ2):c.319C>T (p.Leu107Phe) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 20, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000820061.8

Allele description [Variation Report for NM_172107.4(KCNQ2):c.319C>T (p.Leu107Phe)]

NM_172107.4(KCNQ2):c.319C>T (p.Leu107Phe)

Gene:

KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.319C>T (p.Leu107Phe)

HGVS:

NC_000020.11:g.63446815G>A
NG_009004.2:g.30826C>T
NM_004518.6:c.319C>T
NM_172106.3:c.319C>T
NM_172107.4:c.319C>TMANE SELECT
NM_172108.5:c.319C>T
NM_172109.3:c.319C>T
NP_004509.2:p.Leu107Phe
NP_742104.1:p.Leu107Phe
NP_742105.1:p.Leu107Phe
NP_742106.1:p.Leu107Phe
NP_742107.1:p.Leu107Phe
NC_000020.10:g.62078168G>A
NM_172107.2:c.319C>T

Protein change:

L107F

Links:

dbSNP: rs864321712

NCBI 1000 Genomes Browser:

rs864321712

Molecular consequence:

NM_004518.6:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.319C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000960755	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 20, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27535030, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000960755

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 20, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical and genetic features of 13 Spanish patients with KCNQ2 mutations.

Hortigüela M, Fernández-Marmiesse A, Cantarín V, Gouveia S, García-Peñas JJ, Fons C, Armstrong J, Barrios D, Díaz-Flores F, Tirado P, Couce ML, Gutiérrez-Solana LG.

J Hum Genet. 2017 Feb;62(2):185-189. doi: 10.1038/jhg.2016.104. Epub 2016 Aug 18.

PubMed [citation]

PMID:: 27535030

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000960755.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt KCNQ2 protein function. ClinVar contains an entry for this variant (Variation ID: 219241). This missense change has been observed in individual(s) with benign familial neonatal seizures and clinical features of neonatal epileptic encephalopathy (PMID: 27535030; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 107 of the KCNQ2 protein (p.Leu107Phe).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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